Loss-of-function variants in ADCY3 increase risk of obesity and type 2 diabetes. (February 2018)

• Record Type: Journal Article
• Authors: Grarup, Niels; Moltke, Ida; Andersen, Mette; Dalby, Maria; Vitting-Seerup, Kristoffer; Kern, Timo; Mahendran, Yuvaraj; Jørsboe, Emil; Larsen, Christina; Dahl-Petersen, Inger; Gilly, Arthur; Suveges, Daniel; Dedoussis, George; Zeggini, Eleftheria; Pedersen, Oluf; Andersson, Robin; Bjerregaard, Peter; Jørgensen, Marit; Albrechtsen, Anders; Hansen, Torben
• Is Part Of: Nature genetics. Volume 50:Number 2(2018)
• Page Start: 172
• Page End: 174
• Publication Date: 2018-02
• Subjects: Human genetics -- Periodicals; 576.505
• DOI: 10.1038/s41588-017-0022-7
• Languages: English
• ISSNs: 1061-4036

Abstract

Abstract We have identified a variant inADCY3 (encoding adenylate cyclase 3) associated with markedly increased risk of obesity and type 2 diabetes in the Greenlandic population. The variant disrupts a splice acceptor site, and carriers have decreasedADCY3 RNA expression. Additionally, we observe an enrichment of rareADCY3 loss-of-function variants among individuals with type 2 diabetes in trans-ancestry cohorts. These findings provide new information on disease etiology relevant for future treatment strategies. Individuals from a Greenlandic Inuit population with homozygous loss-of-function variants inADCY3 (adenylate cyclase 3) have increased risk for obesity and type 2 diabetes. Carriers of rareADCY3 variants in trans-ancestry populations also show increased association with type 2 diabetes.